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Background: Digital cognitive tests offer several potential advantages over established paper-pencil tests but have not yet been fully evaluated for the clinical evaluation of mild cognitive impairment.Objective: The NeuroCognitive Performance Test (NCPT) is a web-based, self-directed, modular battery intended for repeated assessments of multiple cognitive domains. Our objective was to examine its relationship with the Alzheimer's Disease Assessment Scale-Cognition Subscale (ADAS-Cog) and Mini-Mental State Examination (MMSE) as well as with established paper-pencil tests of cognition and daily functioning in mild cognitive impairment (MCI).Methods: We used Spearman correlations, regressions and principal components analysis followed by a factor analysis (varimax rotated) to examine our objectives.Results: In MCI subjects, the NCPT composite is significantly correlated with both a composite measure of established tests (r = 0.78, p < 0.0001) as well as with the ADAS-Cog (r = -0.55, p < 0.0001). Both NCPT and paper-pencil test batteries had a similar factor structure that included a large "g" component with a high eigenvalue. The correlation for the analogous tests (e.g., Trails A and B, learning memory tests) were significant (p < 0.0001). Further, both the NCPT and established tests significantly (p < 0.0001) predicted the University of California San Diego Performance-Based Skills Assessment and Functional Activities Questionnaire, measures of daily functioning.Conclusion: The NCPT, a web-based, self-directed, computerized test, shows high concurrent validity with established tests and hence offers promise for use as a research or clinical tool in MCI. Despite limitations such as a relatively small sample, absence of control group and cross-sectional nature, these findings are consistent with the growing literature on the promise of self-directed, web-based cognitive assessments for MCI. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is the leading cause of dementia in the world. It affects 6 million people in the United States and 50 million people worldwide. Alzheimer's disease is characterized by the accumulation of amyloid-β plaques (Aβ), an increase in tau protein neurofibrillary tangles, and a loss of synapses. Since the 1990s, removing and reducing Aβ has been the focus of Alzheimer's treatment and prevention research. The accumulation of Aβ can lead to oxidative stress, inflammation, neurotoxicity, and eventually apoptosis. These insults impair signaling systems in the brain, potentially leading to memory loss and cognitive decline. Aniracetam is a safe, effective, cognitive-enhancing drug that improves memory in both human and animal studies. Aniracetam may prevent the production and accumulation of Aβ by increasing α-secretase activity through two distinct pathways: 1) increasing brain derived neurotrophic factor expression and 2) positively modulating metabotropic glutamate receptors. This is the first paper to propose an evidence-based model for aniracetam reducing the accumulation and production of Aβ. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) plagues 6.5 million Americans 65+, yet treatments are lacking. The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet has been developed to address the expansive impact of dementias on the general public. This systematic review evaluated the impact of the MIND diet on cognition in those with pathologies across the dementia spectrum. Objective: To evaluate the application of the MIND diet for prevention and/or treatment of dementia. Methods: PubMed was used to conduct a search using the MIND diet and terms related to cognition. Articles were excluded if they were published prior to 2018, studied a population without dementia or significant risk factors, or did not include those 65 +. The overall quality of each source was analyzed based on the cognitive test(s) used, the selection of subjects, and the sample size. Results: The search generated 33 papers, which yielded 11 articles after screening. Of these studies, one was conducted on those with mild cognitive impairment, one with AD, two with general dementia, and seven with at-risk individuals. All the studies found a positive correlation between adherence and some form of cognitive functioning, but results were mixed for specific cognitive domains. Conclusions: These findings suggest that the MIND diet may be a useful long-term treatment option for those with various dementia pathologies. However, more research is needed on subjects with onset dementias. Additionally, there is a need for more research into the mechanisms behind the common comorbidities. [ABSTRACT FROM AUTHOR]

Background: Mnemonic discrimination is the behavioral ability stemming from pattern separation, which is the neural process of establishing independent and non-overlapping new memories. Over the past two decades, its assessment in various populations has contributed to a better conceptual understanding of age-related memory decline. Objective: To assess the clinical relevance of mnemonic discrimination in the memory clinics setting. Methods: This retrospective study was performed in 90 patients with a Mini-Mental State Examination (MMSE)>18 who consulted our memory clinic for the first time. All patients were tested with the Mnemonic Similarity Task, a freely available computerized test. Global cognitive function, executive function, visuoconstructional abilities, and verbal and visual episodic memory were also collected, together with the diagnosis after the initial clinical assessment (subjective cognitive complaint [SCC], mild cognitive impairment [MCI], or mild dementia). Results: Mnemonic discrimination performance was correlated with global cognitive function, executive function, and visual and verbal episodic memory scores, independent of age. It discriminated patients with SCC from those with MCI (amnestic or non-amnestic) with moderate accuracy (AUC = 0.77-0.78), similar to MMSE and the Frontal Assessment Battery (AUC = 0.74-0.84). Mnemonic discrimination performance did not distinguish between amnestic and non-amnestic MCI and the variability of the measure was important within groups. Conclusion: Mnemonic discrimination performance involves many cognitive domains and discriminates between patients with SCC and MCI with performance equivalent to "paper-and-pencil" screening tests. Further dedicated prospective studies will determine whether this task is of interest beyond research purposes, as a diagnostic or screening tool in primary care. [ABSTRACT FROM AUTHOR]

Background: Evidence summaries for efficacy and safety of frequently employed treatments of Alzheimer's disease (AD) are sparse.Objective: We aimed to perform an updated umbrella review to identify an efficacious and safe treatment for AD patients.Methods: We conducted a search for meta-analyses and systematic reviews on the Embase, PubMed, The Cochrane Library, and Web of Science to address this knowledge gap. We examined the cognitive functions, behavioral symptoms, global clinical assessment, and Activities of Daily Living as efficacy endpoints, and the incidence of adverse events as safety profiles.Results: Sixteen eligible papers including 149 studies were included in the umbrella review. The results showed that AChE inhibitors (donepezil, galantamine, rivastigmine, Huperzine A), Ginkgo biloba, and cerebrolysin appear to be beneficial for cognitive, global performances, and activities of daily living in patients with AD. Furthermore, anti-Aβ agents are unlikely to have an important effect on slowing cognitive or functional impairment in mild to moderate AD.Conclusion: Our study demonstrated that AChE inhibitors, Ginkgo biloba, and cerebrolysin are the optimum cognitive and activities of daily living medication for patients with AD. [ABSTRACT FROM AUTHOR]

Current research trends emphasize complex models of cognitive outcomes, with multiple, interacting predictors, including factors amenable to interventions toward sustaining healthy cognitive aging. Such models often require advanced analysis techniques. The article by Stark et al., 'Partial least squares regression analysis of Alzheimer's disease biomarkers, modifiable health variables, and cognitive change in older adults with mild cognitive impairment', uses partial least squares regression to examine the associations to memory and executive change of 29 biomarker and demographic variables. This commentary discusses the significance of their results and methods within the context of current research foci. [ABSTRACT FROM AUTHOR]

The increase in the incidence of dementia over the last century correlates strongly with the increases in post-reproductive lifespan during this time. As post-reproductive lifespan continues to increase it is likely that the incidence of dementia will also increase unless therapies are developed to prevent, slow or cure dementia. A growing body of evidence implicates age-related endocrine dyscrasia and the length of time that the brain is subjected to this endocrine dyscrasia, as a key causal event leading to the cognitive decline associated with aging and Alzheimer's disease (AD), the major form of dementia in our society. In particular, the elevations in circulating gonadotropins, resulting from the loss of gonadal sex hormone production with menopause and andropause, appear central to the development of AD neuropathology and cognitive decline. This is supported by numerous cell biology, preclinical animal, and epidemiological studies, as well as human clinical studies where suppression of circulating luteinizing hormone and/or follicle-stimulating hormone with either gonadotropin-releasing hormone analogues, or via physiological hormone replacement therapy, has been demonstrated to halt or significantly slow cognitive decline in those with AD. This review provides an overview of past and present studies demonstrating the importance of hypothalamic-pituitary-gonadal hormone balance for normal cognitive functioning, and how targeting age-related endocrine dyscrasia with hormone rebalancing strategies provides an alternative treatment route for those with AD. [ABSTRACT FROM AUTHOR]

Background: The largest identified kindred worldwide with a single mutation causing autosomal-dominant Alzheimer's disease (ADAD) is a family from Antioquia, Colombia, carrying the Presenilin-1 (PSEN1) E280A (Paisa) mutation. The majority of mutation carriers develop dementia, typically commencing in their late 30 s, with a median onset age of 49 years. Cognitive decline is a hallmark feature. Objective: This review synthesizes the existing literature on neuropsychological assessments in PSEN1 E280A mutation carriers throughout their lifespan. We provide a comprehensive overview of cognitive outcomes in this unique population. Methods: We reviewed and integrated the published research, analyzing studies on neuropsychological assessments in PSEN1 E280A carriers. Our focus was on measures of verbal, semantic, episodic, and spatial memory, and encompassed other cognitive domains such as language, attention, visuospatial memory, and executive functioning. Results: Verbal, semantic, episodic, and spatial memory emerged as the most sensitive indicators of preclinical changes in PSEN1 E280A carriers. Inconsistencies were noted in findings from tests assessing language, attention, visuospatial memory, and executive functioning, suggesting potential limitations in detecting early cognitive changes in PSEN1 mutation carriers. Specific cognitive tasks developed for this population proved effective but underutilized. Conclusions: The review underscores the importance of continued test development tailored to detect early cognitive changes in PSEN1 E280A carriers, potentially enhancing ADAD screening. Furthermore, investigating ADAD mutations in children may identify early changes in AD and enhance our understanding of neuropsychological functioning across the lifespan. This synthesis provides valuable insights for researchers, clinicians, and policymakers engaged in the study and management of ADAD. [ABSTRACT FROM AUTHOR]

Background: The Addenbrooke's Cognitive Examination-Revised (ACE-R) is an accessible cognitive tool that supports the early detection of mild cognitive impairment (MCI), Alzheimer's disease (AD), and behavioral variant frontotemporal dementia (bvFTD). Objective: To investigate the diagnostic efficacy of the ACE-R in MCI, AD, and bvFTD through the identification of novel coefficients for differentiation between these diseases. Methods: We assessed 387 individuals: 102 mild AD, 37 mild bvFTD, 87 with amnestic MCI patients, and 161 cognitively unimpaired controls. The Mokken scaling technique facilitated the extraction out of the 26 ACE-R items that exhibited a common latent trait, thereby generating the Mokken scales for the AD group and the MCI group. Subsequently, we performed logistic regression, integrating each Mokken scales with sociodemographic factors, to differentiate between AD and bvFTD, as well as between AD or MCI and control groups. Ultimately, the Receiver Operating Characteristic curve analysis was employed to assess the efficacy of the coefficient's discrimination. Results: The AD-specific Mokken scale (AD-MokACE-R) versus bvFTD exhibited an Area Under the Curve (AUC) of 0.922 (88% sensitivity and specificity). The AD-MokACE-R versus controls achieved an AUC of 0.968 (93% sensitivity, 94% specificity). The MCI-specific scale (MCI-MokACE-R) versus controls demonstrated an AUC of 0.859 (78% sensitivity, 79% specificity). Conclusions: The ACE-R's capacity is enhanced through statistical methods and demographic integration, allowing for accurate differentiation between AD and bvFTD, as well as between MCI and controls. This new method not only reinforces its clinical value in early diagnosis but also surpasses traditional approaches noted in prior studies. [ABSTRACT FROM AUTHOR]

Normally, an adequate cerebral blood flow arrives at individual cerebral neurons in which the blood flow augments activity of intraneuronal mitochondria, which is the source of intraneuronal ATP, the energy source of cerebral neurons. With a decrease in cerebral blood flow that can occur as a function of normal aging phenomena, less blood results in decreased mitochondria, decreased ATP, and a decrease in neuronal activity, which can eventually lead to Alzheimer's disease. It has been found that placement of the omentum directly on an Alzheimer's disease brain can lead to improved cognitive function. [ABSTRACT FROM AUTHOR]

Background: Individuals with type 2 diabetes (T2D) have an increased risk of cognitive symptoms and Alzheimer's disease (AD). Mis-metabolism with aggregation of amyloid-β peptides (Aβ) play a key role in AD pathophysiology. Therefore, human studies on Aβ metabolism and T2D are warranted. Objective: The objective of this study was to examine whether acute hyperglycemia affects plasma Aβ1–40 and Aβ1–42 concentrations in individuals with T2D and matched controls. Methods: Ten participants with T2D and 11 controls (median age, 69 years; range, 66–72 years) underwent hyperglycemic clamp and placebo clamp (saline infusion) in a randomized order, each lasting 4 hours. Aβ1–40, Aβ1–42, and insulin-degrading enzyme (IDE) plasma concentrations were measured in blood samples taken at 0 and 4 hours of each clamp. Linear mixed-effect regression models were used to evaluate the 4-hour changes in Aβ1–40 and Aβ1–42 concentrations, adjusting for body mass index, estimated glomerular filtration rate, and 4-hour change in insulin concentration. Results: At baseline, Aβ1–40 and Aβ1–42 concentrations did not differ between the two groups. During the hyperglycemic clamp, Aβ decreased in the control group, compared to the placebo clamp (Aβ1–40: p = 0.034, Aβ1–42: p = 0.020), IDE increased (p = 0.016) during the hyperglycemic clamp, whereas no significant changes in either Aβ or IDE was noted in the T2D group. Conclusions: Clamp-induced hyperglycemia was associated with increased IDE levels and enhanced Aβ40 and Aβ42 clearance in controls, but not in individuals with T2D. We hypothesize that insulin-degrading enzyme was inhibited during hyperglycemic conditions in people with T2D. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease and mild cognitive impairment (MCI) progress silently, making early diagnosis challenging, especially in less educated populations. The visual paired comparison (VPC) task, utilizing eye-tracking movement (ETM) technology, offers a promising alternative for early detection of memory decline. Objective: This systematic review and meta-analysis evaluated the efficacy of the VPC task, utilizing ETM as a tool for assessing age-related cognitive changes. Methods: A comprehensive search across five databases and grey literature focused on healthy and impaired memory participants assessed through the ETM-based VPC task. The primary outcomes were novelty preference scores and eye movement metrics. The risk of bias of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Random-effects meta-analyses calculated Hedges' g effect size. Sensitivity and specificity of the VPC were meta-analytically pooled. Results: The systematic review included 12 articles, involving 1,022 participants (aged 18 to 90 years, with education ranging from 6.5 to 20.0 years), with a low risk of bias and minimal applicability concerns across all items. Five studies contributed to the meta-analysis, revealing a significant effect favoring the VPC task for recognition memory detection (k = 9, g = –1.03). Pooled sensitivity and specificity analyses demonstrated VPC effectiveness as a recognition memory assessment tool (0.84 and 0.75, respectively). Conclusions: The VPC task, utilizing ETM, may serve as a biomarker for early memory decline detection. Its use as a digital eye-tracking tool presents a possible alternative to traditional tests, warranting further research for application in neurodegenerative disease diagnosis. [ABSTRACT FROM AUTHOR]

Background: Antioxidant diets are considered to be protective factors for cognitive function. However, comprehensive measures of antioxidant diets are lacking. Objective: To examine the association between the Composite Dietary Antioxidant Index (CDAI) and cognitive function in the elderly. Methods: This cross-sectional study included a total of 2,456 participants (≥60 years old) from NHANES 2011–2014. Calculation of CDAI based on 6 minerals and vitamins (manganese, selenium, zinc, vitamins A, C, and E). Cognitive function was measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning sub-test, Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). We also created a composite cognitive z-score to represent global cognition. The statistical analyses we used included multiple linear regression analyses, subgroup analyses, curve-fitting analyses, and threshold effects analyses. Results: After controlling for demographic characteristics, lifestyle factors, and disease history, multivariate linear regression analyses showed that increased CDAI was positively associated with scores on global cognitive function and each cognitive domain (p < 0.05), with subgroup analyses suggesting that this association was more pronounced in stroke patients (p for interaction < 0.05). Curve-fitting analyses and threshold effect analyses showed saturation effects between CDAI and CREAD Test, AFT, and composite Z-score, and an inverted U-shaped relationship with DSST, with inflection points of –1.89, 0.79, 1.13, and 1.77, respectively. Conclusions: Our findings support that higher levels of CDAI are correlated with significantly elevated cognitive function. Maintaining CDAI in an appropriate range may contribute to cognitive health in elderly. [ABSTRACT FROM AUTHOR]

Background: Lipids have a significant impact on the development and functioning of the nervous system, but the sex differences between the association of LDL/HDL, which reflects lipid metabolic status, and cognitive impairment remains unclear. Objective: We aimed to determine if there were sex differences between the association of LDL/HDL and cognitive function in US older adults. Methods: This population-based cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) 2011–2012 and 2013–2014 cycles. The main outcome was poor cognitive performance defined by the Digit Symbol Substitution Test (DSST) < 34 based on published literature. Results: A total of 1,225 participants were included in the study, with a cognitive impairment incidence of 25.6% (314/1,225). Multivariate regression models demonstrated a significant association between cognitive decline and each 1-unit increase in LDL/HDL, after adjusting for all covariates (adjusted odds ratio [OR] = 1.36, 95% confidence interval [CI]: 1.11–1.67). Furthermore, subgroup analysis revealed an interaction between LDL/HDL and cognitive impairment in sex subgroups. Conclusions: LDL/HDL was associated with cognitive impairment in the US older adult population in adjusted models, although the significance of this association was not observed in females. [ABSTRACT FROM AUTHOR]

High dietary intake of saturated fatty acids is a suspected risk factor for neurodegenerative diseases, including Alzheimer's disease (AD). To decipher the causal link behind these associations, high-fat diets (HFD) have been repeatedly investigated in animal models. Preclinical studies allow full control over dietary composition, avoiding ethical concerns in clinical trials. The goal of the present article is to provide a narrative review of reports on HFD in animal models of AD. Eligibility criteria included mouse models of AD fed a HFD defined as > 35% of fat/weight and western diets containing > 1% cholesterol or > 15% sugar. MEDLINE and Embase databases were searched from 1946 to August 2022, and 32 preclinical studies were included in the review. HFD-induced obesity and metabolic disturbances such as insulin resistance and glucose intolerance have been replicated in most studies, but with methodological variability. Most studies have found an aggravating effect of HFD on brain Aβ pathology, whereas tau pathology has been much less studied, and results are more equivocal. While most reports show HFD-induced impairment on cognitive behavior, confounding factors may blur their interpretation. In summary, despite conflicting results, exposing rodents to diets highly enriched in saturated fat induces not only metabolic defects, but also cognitive impairment often accompanied by aggravated neuropathological markers, most notably Aβ burden. Although there are important variations between methods, particularly the lack of diet characterization, these studies collectively suggest that excessive intake of saturated fat should be avoided in order to lower the incidence of AD. [ABSTRACT FROM AUTHOR]

Background: With continuously aging societies, an increase in the number of people with cognitive decline is to be expected. Aside from the development of causative treatments, the successful implementation of prevention strategies is of utmost importance to reduce the high societal burden caused by neurodegenerative diseases leading to dementia among which the most common cause is Alzheimer's disease. Objective: The aim of the Luxembourgish "programme dementia prevention (pdp)" is to prevent or at least delay dementia in an at-risk population through personalized multi-domain lifestyle interventions. The current work aims to provide a detailed overview of the methodology and presents initial results regarding the cohort characteristics and the implementation process. Methods: In the frame of the pdp, an extensive neuropsychological evaluation and risk factor assessment are conducted for each participant. Based on the results, individualized multi-domain lifestyle interventions are suggested. Results: A total number of 450 participants (Mean age = 69.5 years; SD = 10.8) have been screened at different recruitment sites throughout the country, among whom 425 participants (94.4%) met the selection criteria. Conclusions: We provide evidence supporting the feasibility of implementing a nationwide dementia prevention program and achieving successful recruitment of the target population by establishing a network of different healthcare providers. [ABSTRACT FROM AUTHOR]

Background: Recent genetic research identified a protective factor against late-onset Alzheimer's disease (AD) in Caucasians, a variant called rs3747742-C in the TREML2 gene. However, the roles of other TREML2 variants in AD have not been fully explored. Objective: We conducted a focused analysis of 16 TREML2 variants, examining their connection to AD by studying their correlation with cerebrospinal fluid (CSF) proteins, neuroimage, and cognition in the Alzheimer's Disease Neuroimaging Initiative database (ADNI). Methods: A multiple linear regression model was utilized to estimate potential associations between TREML2 genotypes and various endophenotypes in the entire ADNI sample at baseline, with age, gender, years of education, and APOE ɛ4 status included as covariates. To examine changes in clinical outcomes over time, linear mixed-effects models were employed. Results: We found that the SNP rs17328707-A was associated with higher ADNI-VS scores, smaller ventricles, and larger middle temporal volume at baseline. The SNP rs6915083-G was linked to lower CSF t-tau and p-tau levels, and higher CSF Aβ levels. The SNP rs9394766-G was associated with a smaller hippocampus and larger ventricles at baseline. In longitudinal cohorts, the rs6915083-G SNP was associated with changes in ADNI-MEM and ADNI-EF scores, as well as the rate of hippocampal and middle temporal atrophy. Conclusion: Our findings reveal that TREML2 gene variants have different effects on AD. Two variants are protective, while one may be a risk factor. This enhances our understanding of AD genetics and could guide future research and personalized treatments. [ABSTRACT FROM AUTHOR]

Background: Repetitive behaviors (RBs) are a well-known symptom of Alzheimer's disease (AD); however, they have been little studied and have not been the subject of any specific literature review. Objective: To conduct a systematic review of all studies to document RBs in AD. Methods: An extensive literature search combining five databases and a meta-analysis were conducted to investigate the frequency, nature, and cognitive correlates of RBs in AD. Results: Ten studies were included in the review. Seven studies out of ten investigated the frequency of RBs in patients with AD, which ranged from 52.3% to 87%. A meta-analysis showed an overall frequency of 66.3% (95% CI: 55.5; 77.1) of patients exhibiting RBs in AD, but important heterogeneity was observed between studies. Three studies investigated the predominant nature of RBs in AD. Verbal RBs, complex behavioral stereotypies, and simple motor stereotypies have been identified to different degrees depending on the level of dementia. Most verbal RBs are underpinned by episodic memory impairment, while simple motor stereotypies and complex behavioral stereotypies are mostly underpinned by executive dysfunction. Conclusions: The current review seems to suggest that there are two types of mechanisms underpinning RBs involved in AD. The first is observed especially in the mild stages of the disease and is mediated by episodic memory impairment. The second occurs later and is mediated by executive impairment. Additional studies should be conducted to improve the knowledge about RBs in AD and thus improve their management. Systematic review registration number: PROSPERO 2022: CRD42022310027 [ABSTRACT FROM AUTHOR]

Background: Several clinical trials have examined diet and physical activity lifestyle changes as mitigation strategies for risk factors linked to cognitive decline and dementias such as Alzheimer's disease. However, the ability to modify these behaviors longer term, to impact cognitive health has remained elusive. Objective: The MedWalk trial's primary aim is to investigate whether longer-term adherence to a Mediterranean-style diet and regular walking, delivered through motivational interviewing and cognitive-behavioral therapy (MI-CBT), can reduce age-associated cognitive decline and other dementia risk factors in older, independently living individuals without cognitive impairment. Methods: MedWalk, a one-year cluster-randomized controlled trial across two Australian states, recruited 60–90-year-old people from independent living retirement villages and the wider community. Participants were assigned to either the MedWalk intervention or a control group (maintaining their usual diet and physical activity). The primary outcome is 12-month change in visual memory and learning assessed from errors on the Paired Associates Learning Task of the Cambridge Neuropsychological Test Automated Battery. Secondary outcomes include cognition, mood, cardiovascular function, biomarkers related to nutrient status and cognitive decline, MI-CBT effectiveness, Mediterranean diet adherence, physical activity, quality of life, cost-effectiveness, and health economic evaluation. Progress and Discussion: Although COVID-19 impacts over two years necessitated a reduced timeline and sample size, MedWalk retains sufficient power to address its aims and hypotheses. Baseline testing has been completed with 157 participants, who will be followed over 12 months. If successful, MedWalk will inform interventions that could substantially reduce dementia incidence and ameliorate cognitive decline in the community. Trial registration: Registered on the Australia New Zealand Clinical Trials Registry ANZCTR 12620000978965 (). [ABSTRACT FROM AUTHOR]

Background: Pork provides higher levels of several nutrients important for cognitive maintenance in older adults. A pilot clinical study suggests the addition of moderate amounts of pork to a Mediterranean-style diet improves cognition in older adults. There is an absence of observational research that isolates effects of pork from other red meats. Objective: To examine the relationship of pork intake on cognitive performance in older adults. Methods: Cross-sectional data from the U.S. National Health and Nutrition Examination Survey (NHANES) 2011–2014 cycles were used in these analyses. Pork intake was assessed using data from two non-consecutive 24-h dietary recalls. Cognitive function was assessed by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning, CERAD Delayed Recall, Animal Fluency, and Digital Substitution tests. Statistical analyses were adjusted for sample weighting and survey design variables to account for the complex design. Student t-tests (continuous variables) and Pearson chi-squared tests (categorical variables) were employed to compare participant characteristics between the low and normal cognitive performance groups. Logistic regression was used to determine the relationship of pork intake (low, medium, and high) with prevalence of low cognitive performance, with the non-consumer group as the referent category. Results: Pork intake was not beneficially or detrimentally associated performance on the any of the cognitive tests in both the crude and multivariate models (p > 0.05). Conclusions: Prospective cohort investigations and larger/longer-term clinical trials are needed to fully elucidate effects of pork intake on cognition in older adults. [ABSTRACT FROM AUTHOR]

Background: Handwriting is a complex process involving fine motor skills, kinesthetic components, and several cognitive domains, often impaired by Alzheimer's disease (AD). Objective: Provide a systematic review of handwriting changes in AD, highlighting the effects on motor, visuospatial and linguistic features, and to identify new research topics. Methods: A search was conducted on PubMed, Scopus, and Web of Science to identify studies on AD and handwriting. The review followed PRISMA norms and analyzed 91 articles after screening and final selection. Results: Handwriting is impaired at all levels of the motor-cognitive hierarchy in AD, particularly in text, with higher preservation of signatures. Visuospatial and linguistic features were more affected. Established findings for motor features included higher variability in AD signatures, higher in-air/on-surface time ratio and longer duration in text, longer start time/reaction time, and lower fluency. There were conflicting findings for pressure and velocity in motor features, as well as size, legibility, and pen lifts in general features. For linguistic features, findings were contradictory for error patterns, as well as the association between agraphia and severity of cognitive deficits. Conclusions: Further re-evaluation studies are needed to clarify the divergent results on motor, general, and linguistic features. There is also a lack of research on the influence of AD on signatures and the effect of AD variants on handwriting. Such research would have an impact on clinical management (e.g., for early detection and patient follow-up using handwriting tasks), or forensic examination aimed at signatory identification. [ABSTRACT FROM AUTHOR]

Background: TOMM40 '523 has been associated with cognitive performance and risk for developing Alzheimer's disease independent of the effect of APOE genotype. Few studies have considered the longitudinal effect of this genotype on change in cognition over time. Objective: Our objective was to evaluate the relationship between TOMM40 genotype status and change in cognitive performance in the TOMMORROW study, which was designed to prospectively evaluate an algorithm that includes TOMM40 '523 for genetic risk for conversion to mild cognitive impairment. Methods: We used latent growth curve models to estimate the effect of TOMM40 allele carrier (short, very long) status on the intercept and slope of change in cognitive performance in four broad cognitive domains (attention, memory, executive function, and language) and a combined overall cognitive score over 30 months. Results: TOMM40 very long allele carriers had significantly lower baseline performance for the combined overall cognitive function score (B = –0.088, p = 0.034) and for the executive function domain score (B = –0.143, p = 0.013). Slopes for TOMM40 very long carriers had significantly greater increases over time for the executive function domain score only. In sensitivity analyses, the results for executive function were observed in participants who remained clinically stable, but not in those who progressed clinically over the study duration. Conclusions: Our results add to the growing body of evidence that TOMM40, in the absence of APOEɛ4, may contribute to cognitive changes with aging and dementia and support the view that mitochondrial function is an important contributor to Alzheimer's disease risk. [ABSTRACT FROM AUTHOR]

Background: Traditional board games can entail significant skills encompassing several cognitive functions across different domains. Therefore, they may potentially represent effective cognitive interventions in the aging population with or without Alzheimer's disease or other types of dementia. Objective: We aimed at verifying the hypothesis that traditional board games can prevent or slow down cognitive decline, through a systematic review on traditional board games and dementia. Methods: We searched five databases with tailored search strings. We included studies assessing the impact of board games on elderly subjects at risk of or suffering from cognitive impairment, or subjects with cognitive impairment irrespective of age. Studies where the effect of board games was not separated by cards or other games were excluded. A meta-analysis was performed for specific cognitive and non-cognitive outcomes. Results: Board games improved mental function, as measured by Montreal Cognitive Assessment (p = 0.003) and Mini-Mental State Examination (p = 0.02). Ska and Go improved Trail Making Test –A, while Mahjong improved executive functions. There was no consistent effect across different games on Digit Span or Categorical Fluency. Chess improved quality of life measured with the WHO-QoL-OLD scale (p < 0.00001). Mahjong temporarily improved depressive symptoms. Go increased BDNF levels and left middle temporal gyrus and bilateral putamen metabolism. Conclusions: Traditional board games may slow global cognitive decline and improve the quality of life in elderly subjects. Different games have varying impacts on specific cognitive domains, possibly mediated by functional and biological factors. [ABSTRACT FROM AUTHOR]

Background: Greater cardiovascular burden and peripheral inflammation are associated with dysexecutive neuropsychological profiles and a higher likelihood of conversion to vascular dementia. The digital clock drawing test (dCDT) is useful in identifying neuropsychological dysfunction related to vascular etiology. However, the specific cognitive implications of the combination of cardiovascular risk, peripheral inflammation, and brain integrity remain unknown. Objective: We aimed to examine the role of cardiovascular burden, inflammation, and MRI-defined brain integrity on dCDT latency and graphomotor metrics in older adults. Methods: 184 non-demented older adults (age 69±6, 16±3 education years, 46% female, 94% white) completed dCDT, vascular assessment, blood draw, and brain MRI. dCDT variables of interest: total completion time (TCT), pre-first hand latency, digit misplacement, hour hand distance from center, and clock face area. Cardiovascular burden was calculated using the Framingham Stroke Risk Profile (FSRP-10). Peripheral inflammation markers included interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-alpha, and high sensitivity C-reactive protein. Brain integrity included bilateral entorhinal cortex volume, lateral ventricular volume, and whole brain leukoaraiosis. Results: FSRP-10, peripheral inflammation, and brain integrity explained an additional 14.6% of the variance in command TCT, where FSRP-10 was the main predictor. FSRP-10, inflammatory markers, and brain integrity explained an additional 17.0% in command digit misplacement variance, with findings largely driven by FSRP-10. Conclusion: Subtle graphomotor behavior operationalized using dCDT metrics (i.e., TCT and digit misplacement) is partly explained by cardiovascular burden, peripheral inflammation, and brain integrity and may indicate vulnerability to a disease process. [ABSTRACT FROM AUTHOR]

Background: Cognition and its age-related changes remain vastly understudied in low-income countries (LICs), despite evidence suggesting that cognitive decline among aging low-income populations is a rapidly increasing disease burden often occurring at younger ages as compared to high-income countries (HICs). Objective: We examine patterns of cognition among men and women, 45 + years old, living in rural Malawi. We analyze how key socioeconomic characteristics predict levels of cognition and its changes as individuals get older. Methods: Utilizing the Mature Adults Cohort of the Malawi Longitudinal Study of Families and Health (MLSFH-MAC) collected during 2012–2017, we estimate standard regression models to analyze predictors of the age- and sex-specific levels and longitudinal changes in cognition. Cognition is assessed with a screening instrument that is adapted to this low-literacy context and measures different domains such as language, attention, or executive functioning. Results: Women have lower levels of cognition than men, a pattern in stark contrast to findings in HICs. Schooling and socioeconomic status increase the probability of having consistently high performance during the cognitive assessment. Cognitive decline accelerates with age and is detectable already at mid-adult ages (45–55 years). Despite lower levels of cognitive function observed among women, the pace of decline with age is similar for both genders. Conclusion: Women are particularly affected by poor cognition in this context. The study emphasizes the importance of prioritizing cognitive health and research on cognition among older individuals in sub-Saharan Africa LICs, to which relatively little health care resources continue to be allocated. [ABSTRACT FROM AUTHOR]

Background: Genetic scores for late-onset Alzheimer's disease (LOAD) have been associated with preclinical cognitive decline and biomarker variations. Compared with an overall polygenic risk score (PRS), a pathway-specific PRS (p-PRS) may be more appropriate in predicting a specific biomarker or cognitive component underlying LOAD pathology earlier in the lifespan. Objective: In this study, we leveraged longitudinal data from the Wisconsin Registry for Alzheimer's Prevention and explored changing patterns in cognition and biomarkers at various age points along six biological pathways. Methods: PRS and p-PRSs with and without APOE were constructed separately based on the significant SNPs associated with LOAD in a recent genome-wide association study meta-analysis and compared to APOE alone. We used a linear mixed-effects model to assess the association between PRS/p-PRSs and cognitive trajectories among 1,175 individuals. We also applied the model to the outcomes of cerebrospinal fluid biomarkers in a subset. Replication analyses were performed in an independent sample. Results: We found p-PRSs and the overall PRS can predict preclinical changes in cognition and biomarkers. The effects of PRS/p-PRSs on rate of change in cognition, amyloid-β, and tau outcomes are dependent on age and appear earlier in the lifespan when APOE is included in these risk scores compared to when APOE is excluded. Conclusion: In addition to APOE, the p-PRSs can predict age-dependent changes in amyloid-β, tau, and cognition. Once validated, they could be used to identify individuals with an elevated genetic risk of accumulating amyloid-β and tau, long before the onset of clinical symptoms. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence that supplementation of S-adenosylmethionine (SAM) can improve cognitive function in animals and humans, although the outcomes are not always inconsistent. Objective: We conducted a systematic review and meta-analysis to evaluate the correlation between SAM supplementation and improved cognitive function. Methods: We searched studies in the PubMed, Cochrane Library, Embase, Web of Science, and Clinical Trials databases from January 1, 2002 to January 1, 2022. Risk of bias was assessed using the Cochrane risk of bias 2.0 (human studies) and the Systematic Review Center for Laboratory Animal Experimentation risk of bias (animal studies) tools; and evidence quality was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation. STATA software was employed to perform meta-analysis, and the random-effects models was used to evaluate the standardized mean difference with 95% confidence intervals. Results: Out of the 2,375 studies screened, 30 studies met the inclusion criteria. Meta-analyses of animal (p = 0.213) and human (p = 0.047) studies showed that there were no significant differences between the SAM supplementation and control groups. The results of the subgroup analyses showed that the animals aged ≤8 weeks (p = 0.027) and the intervention duration >8 weeks (p = 0.009) were significantly different compared to the controls. Additionally, the Morris water maze test (p = 0.005) used to assess the cognitive level of the animals revealed that SAM could enhance spatial learning and memory in animals. Conclusion: SAM supplementation showed no significant improvement in cognition. Therefore, further studies are needed to assess the effectiveness of SAM supplementation. [ABSTRACT FROM AUTHOR]

Background: Macular pigment optical density (MPOD) remains an indispensable biomarker to measure fruit and vegetable intake, with a biologically plausible correlation to vision and cognition. However, evidence in the sub-Saharan regions, including Ghana, is lacking. Objective: This study explored dietary carotenoid intake on MPOD and its influence on cognitive and visual function in a healthy Ghanaian sample. Methods: The MPOD of 301 healthy subjects (aged 21.1±1.9 years) was evaluated using the customized Macular DensitometerTM. A battery of cognitive tests and standard vision assessments were employed to assess cognition and visual function, respectively. Dietary lutein and zeaxanthin (L and Z) were estimated based on a twenty-four-hour repeated dietary recall. Results: The mean MPOD at 0.5° and 1.0° eccentricities were 0.37±0.16 and 0.34±0.15 optical density units, respectively. Dietary intake of L (4.06±10.54 mg/day) was considerably higher than Z (0.33±2.25 mg/day), with cumulative L+Z estimated at 4.39±11.58 mg/day. MPOD was not significantly influenced by demographic, dietary, and visual measures (p≥0.05). However, after statistical adjustment, we found a small but statistically significant positive relationship between F-A-S phonemic verbal fluency (Unstandardized co-efficient (β) = 0.002, p = 0.016) and the never consumed alcohol category (β= 0.062, p = 0.02) with MPOD. Conclusion: The findings in this population showed significant positive relationships between measures of cognition and no alcohol intake, with MPOD. These findings necessitate dietary education to augment carotenoid intake and limit alcohol intake for better cognitive functioning. [ABSTRACT FROM AUTHOR]

Background: Both sleep deficiencies and Alzheimer's disease (AD) disproportionately affect older African Americans. Genetic susceptibility to AD further compounds risk for cognitive decline in this population. Aside from APOE ɛ4, ABCA7 rs115550680 is the strongest genetic locus associated with late-onset AD in African Americans. While sleep and ABCA7 rs115550680 independently influence late-life cognitive outcomes, we know too little about the interplay between these two factors on cognitive function. Objective: We investigated the interaction between sleep and ABCA7 rs115550680 on hippocampal-dependent cognitive function in older African Americans. Methods: One-hundred fourteen cognitively healthy older African Americans were genotyped for ABCA7 risk (n = 57 carriers of risk "G" allele; n = 57 non-carriers), responded to lifestyle questionnaires, and completed a cognitive battery. Sleep was assessed via a self-reported rating of sleep quality (poor, average, good). Covariates included age and years of education. Results: Using ANCOVA, we found that carriers of the risk genotype who reported poor or average sleep quality demonstrated significantly poorer generalization of prior learning—a cognitive marker of AD—compared to their non-risk counterparts. Conversely, there was no genotype-related difference in generalization performance in individuals who reported good sleep quality. Conclusion: These results indicate that sleep quality may be neuroprotective against genetic risk for AD. Future studies employing more rigorous methodology should investigate the mechanistic role of sleep neurophysiology in the pathogenesis and progression of AD associated with ABCA7. There is also need for the continued development of non-invasive sleep interventions tailored to racial groups with specific AD genetic risk profiles. [ABSTRACT FROM AUTHOR]

Background: Detecting clinically meaningful changes in instrumental activities of daily living (IADL) at the earliest stages of Alzheimer's disease (AD) is critical. Objective: The objective of this exploratory study was to examine the cross-sectional relationship between a performance-based IADL test, the Harvard Automated Phone Task (APT), and cerebral tau and amyloid burden in cognitively normal (CN) older adults. Methods: Seventy-seven CN participants underwent flortaucipir tau and Pittsburgh Compound B amyloid PET. IADL were assessed using the three Harvard APT tasks: prescription refill (APT-Script), health insurance company call (APT-PCP), and bank transaction (APT-Bank). Linear regression models were used to determine associations between each APT task and entorhinal cortex, inferior temporal, or precuneus tau with or without an interaction with amyloid. Results: Significant associations were found between APT-Bank task rate and interaction between amyloid and entorhinal cortex tau, and APT-PCP task and interactions between amyloid and inferior temporal and precuneus tau. No significant associations were found between the APT tasks and tau or amyloid alone. Conclusion: Our preliminary findings suggest an association between a simulated real-life IADL test and interactions of amyloid and several regions of early tau accumulation in CN older adults. However, some analyses were underpowered due to the small number of participants with elevated amyloid, and findings should be interpreted with caution. Future studies will further explore these associations cross-sectionally and longitudinally in order to determine whether the Harvard APT can serve as a reliable IADL outcome measure for preclinical AD prevention trials and ultimately in the clinic setting. [ABSTRACT FROM AUTHOR]

Background: Discovering patterns of cognitive domains and characterizing how these patterns associate with other risk factors and biomarkers can improve our understanding of the determinants of cognitive aging. Objective: To discover patterns of cognitive domains using neuropsychological test results in Long Life Family Study (LLFS) and characterize how these patterns associate with aging markers. Methods: 5,086 LLFS participants were administered neuropsychological tests at enrollment. We performed a cluster analysis of six baseline neuropsychological test scores and tested the association between the identified clusters and various clinical variables, biomarkers, and polygenic risk scores using generalized estimating equations and the Chi-square test. We used Cox regression to correlate the clusters with the hazard of various medical events. We investigated whether the cluster information could enhance the prediction of cognitive decline using Bayesian beta regression. Results: We identified 12 clusters with different cognitive signatures that represent profiles of performance across multiple neuropsychological tests. These signatures significantly correlated with 26 variables including polygenic risk scores, physical and pulmonary functions, and blood biomarkers and were associated with the hazard of mortality (p < 0.01), cardiovascular disease (p = 0.03), dementia (p = 0.01), and skin cancer (p = 0.03). Conclusion: The identified cognitive signatures capture multiple domains simultaneously and provide a holistic vision of cognitive function, showing that different patterns of cognitive function can coexist in aging individuals. Such patterns can be used for clinical intervention and primary care. [ABSTRACT FROM AUTHOR]

Background: Some oldest-old individuals can maintain superior cognition despite advanced age. Little is known about the neuropathological changes in the brains of oldest-old superior cognitive performers. Objective: Our objective was to examine the associations between Alzheimer's disease (AD) and non-AD neuropathologic features in relation to superior cognitive performance in oldest-old individuals. Methods: We analyzed brain autopsy data from 102 participants with normal cognition from The 90+ Study. Superior global cognitive performers (SGCP) were defined as having Mini-Mental State Examination (MMSE) score ≥28 in the last visit 12 to 2 months before death. To examine the associations between individual and multiple comorbid neuropathologic features with SGCP status we used multiple logistic regression models adjusting for age, sex, and education. Results: Alzheimer's disease neuropathological change (ADNC) and low levels of vascular pathologic change were not associated with superior cognition. In contrast, participants with limbic (OR = 8.37; 95% CI: 1.48–47.44) and neocortical (OR = 10.80;95% CI: 1.03–113.82) Lewy body disease (LBD), or with hippocampal sclerosis (HS) (OR = 5.28; 95% CI: 1.10–25.47) were more likely to be non-SGCP. High total burden of multiple comorbid neuropathologic features was associated with a lower likelihood of being SGCP. Conclusion: Oldest-old superior cognitive performers were resilient to ADNC and low levels of vascular pathologic change and were resistant to non-AD neurodegenerative changes and multiple comorbid neuropathologic features. Understanding the factors underlying the ability of superior cognitive performers to resist these changes might provide useful insights on maintenance of superior cognition despite advanced age. [ABSTRACT FROM AUTHOR]

Background: Cerebral small vessel disease (CSVD) has been suggested to contribute to the pathogenesis of Alzheimer's disease (AD). Objective: This study aimed to comprehensively investigated the associations of CSVD burden with cognition and AD pathologies. Methods: A total of 546 non-demented participants (mean age, 72.1 years, range, 55–89; 47.4% female) were included. The longitudinal neuropathological and clinical correlates of CSVD burden were assessed using linear mixed-effects and Cox proportional-hazard models. Partial least squares structural equation model (PLS-SEM) was used to assess the direct and indirect effects of CSVD burden on cognition. Results: We found that higher CSVD burden was associated with worse cognition (MMSE, β= –0.239, p = 0.006; MoCA, β= –0.493, p = 0.013), lower cerebrospinal fluid (CSF) Aβ level (β= –0.276, p < 0.001) and increased amyloid burden (β= 0.048, p = 0.002). In longitudinal, CSVD burden contributed to accelerated rates of hippocampus atrophy, cognitive decline, and higher risk of AD dementia. Furthermore, as the results of PLS-SEM, we observed both significant direct and indirect impact of advanced age (direct, β= –0.206, p < 0.001; indirect, β= –0.002, p = 0.043) and CSVD burden (direct, β= –0.096, p = 0.018; indirect, β= –0.005, p = 0.040) on cognition by Aβ-p-tau-tau pathway. Conclusion: CSVD burden could be a prodromal predictor for clinical and pathological progression. Simultaneously, we found that the effects were mediated by the one-direction-only sequence of pathological biomarker changes starting with Aβ, through abnormal p-tau, and neurodegeneration. [ABSTRACT FROM AUTHOR]

Background: Fine particulate matter (PM2.5) and nitrogen dioxide (NO2) measures of ambient air pollution are associated with accelerated age-related cognitive impairment, and Alzheimer's disease and related dementias (ADRD). Objective: We examined associations between air pollution, four cognitive factors, and the moderating role of apolipoprotein E (APOE) genotype in the understudied period of midlife. Methods: Participants were ∼1,100 men in the Vietnam Era Twin Study of Aging. Baseline cognitive assessments were from 2003 to 2007. Measures included past (1993–1999) and recent (3 years prior to baseline assessment) PM2.5 and NO2 exposure, in-person assessment of episodic memory, executive function, verbal fluency, and processing speed, and APOE genotype. Average baseline age was 56 years with a 12-year follow-up. Analyses adjusted for health and lifestyle covariates. Results: Performance in all cognitive domains declined from age 56 to 68. Higher PM2.5 exposures were associated with worse general verbal fluency. We found significant exposure-by-APOE genotype interactions for specific cognitive domains: PM2.5 with executive function and NO2 with episodic memory. Higher PM2.5 exposure was related to worse executive function in APOE ɛ4 carriers, but not in non-carriers. There were no associations with processing speed. Conclusion: These results indicate negative effects of ambient air pollution exposure on fluency alongside intriguing differential modifications of cognitive performance by APOE genotype. APOE ɛ4 carriers appeared more sensitive to environmental differences. The process by which air pollution and its interaction with genetic risk for ADRD affects risk for later life cognitive decline or progression to dementia may begin in midlife. [ABSTRACT FROM AUTHOR]

Background: Dementia prevention is a global health priority, and there is emerging evidence to support associations between individual modifiable health behaviors and cognitive function and dementia risk. However, a key property of these behaviors is they often co-occur or cluster, highlighting the importance of examining them in combination. Objective: To identify and characterize the statistical approaches used to aggregate multiple health-related behaviors/modifiable risk factors and assess associations with cognitive outcomes in adults. Methods: Eight electronic databases were searched to identify observational studies exploring the association between two or more aggregated health-related behaviors and cognitive outcomes in adults. Results: Sixty-two articles were included in this review. Fifty articles employed co-occurrence approaches alone to aggregate health behaviors/other modifiable risk factors, eight studies used solely clustering-based approaches, and four studies used a combination of both. Co-occurrence methods include additive index-based approaches and presenting specific health combinations, and whilst simple to construct and interpret, do not consider the underlying associations between co-occurring behaviors/risk factors. Clustering-based approaches do focus on underlying associations, and further work in this area may aid in identifying at-risk subgroups and understanding specific combinations of health-related behaviors/risk factors of particular importance in the scope of cognitive function and neurocognitive decline. Conclusion: A co-occurrence approach to aggregating health-related behaviors/risk factors and exploring associations with adult cognitive outcomes has been the predominant statistical approach used to date, with a lack of research employing more advanced statistical methods to explore clustering-based approaches. [ABSTRACT FROM AUTHOR]

Background: People with mild cognitive impairment (MCI) need to prevent the further decline of their cognitive functions, and one way to do so is by learning a foreign language. Objective: This study describes the development of a protocol for a novel, non-pharmacological intervention for people with MCI that seeks to prevent or reduce cognitive decline by teaching English through songs. Methods: The development of this protocol follows a mixed-methodology approach, consisting of three stages: 1) development of the protocol of the intervention, 2) a randomized controlled trial study with two arms over six months that includes an intervention group and a control group, and 3) the evaluation of the protocol by trainers. In the second stage, we recruited a total of 128 people with MCI from the five participating countries of this study (Greece, Spain, Croatia, Slovenia, and Italy). This educational program will assess three main outcomes after 6 months of the English Lessons with the Use of Songs for People with Mild Cognitive Impairment (E.L.So.M.C.I.) workshops. Results: Our primary outcome will hopefully be an improvement in general cognition in the intervention group compared to the control group from baseline to 6 months follow-up. Secondary outcomes include a decrease in participants' anxiety and depression and an improvement in their quality of life. Development of English language skills is the last outcome. [ABSTRACT FROM AUTHOR]

Background: It is now acknowledged that Alzheimer's disease (AD) processes are present decades before the onset of clinical symptoms, but it remains unknown whether lifestyle factors can protect against these early AD processes in mid-life. Objective: We asked whether modifiable lifestyle activities impact cognition in middle-aged individuals who are cognitively healthy, but at risk for late life AD. Participants (40–59 years) completed cognitive and clinical assessments at baseline (N = 206) and two years follow-up (N = 174). Methods: Mid-life activities were measured with the Lifetime of Experiences Questionnaire. We assessed the impact of lifestyle activities, known risk factors for sporadic late-onset AD (Apolipoprotein E ɛ4 allele status, family history of dementia, and the Cardiovascular Risk Factors Aging and Dementia score), and their interactions on cognition. Results: More frequent engagement in physically, socially, and intellectually stimulating activities was associated with better cognition (verbal, spatial, and relational memory), at baseline and follow-up. Critically, more frequent engagement in these activities was associated with stronger cognition (verbal and visuospatial functions, and conjunctive short-term memory binding) in individuals with family history of dementia. Impaired visuospatial function is one of the earliest cognitive deficits in AD and has previously associated with increased AD risk in this cohort. Additionally, conjunctive memory functions have been found impaired in the pre-symptomatic stages of AD. Conclusion: These findings suggest that modifiable lifestyle activities offset cognitive decrements due to AD risk in mid-life and support the targeting of modifiable lifestyle activities for the prevention of AD. [ABSTRACT FROM AUTHOR]

Background: The CERAD Word List Memory Test (WLMT) is widely used in the assessment of older adults with suspected dementia. Although normative data of the WLMT exist in many different regions of the world, normative data based on large population-based cohorts from the Scandinavian countries are lacking.Objective: To develop normative data for the WLMT based on a large population-based Norwegian sample of healthy older adults aged 70 years and above, stratified by age, gender, and education.Methods: A total of 6,356 older adults from two population-based studies in Norway, HUNT4 70 + and HUNT4 Trondheim 70+, were administered the WLMT. Only persons with normal cognitive function were included. We excluded persons with a diagnosis of mild cognitive impairment (MCI) and dementia, and persons with a history of stroke and/or depression. This resulted in 3,951 persons aged between 70 and 90 years, of whom 56.2% were females. Regression-based normative data were developed for this sample.Results: Age, gender, and education were significant predictors of performance on the WLMT list-learning subtests and the delayed recall subtest, i.e., participants of younger age, female sex, and higher education level attained higher scores compared to participants of older age, male sex, and lower level of education.Conclusion: Regression-based normative data from the WMLT, stratified by age, gender, and education from a large population-based Norwegian sample of cognitively healthy older adults aged 70 to 90 years are presented. An online norm calculator is available to facilitate scoring of the subtests (in percentiles and z-scores). [ABSTRACT FROM AUTHOR]

Possin and Rosen provide a robust commentary exploring the challenges of using caregivers as cognitive testers. Informants have an important and often overlooked role in diagnosing cognitive impairment. O'Caoimh et al. show they can support cognitive screening in advance of clinic, suggesting new research avenues including the potential for home-monitoring. Although concerns testing may engender bias, introduce practice effects, and impact patient autonomy are valid and require examination, these should be viewed in light of patient preference, clinical need, and the broader ethics of assessing dementia. The importance of distinguishing concerns over accuracy and ethical appropriateness is also discussed. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment and dementia may result from a combination of modifiable and nonmodifiable risk and protective factors, such as the environment, educational attainment, time devoted to cognitively stimulating activities, and physical activity.Objective: This study aimed to investigate the mediating role of sociodemographic characteristics and lifestyle factors in the years of education and cognitive performance in Peruvian adults.Methods: This cross-sectional study included 1,478 subjects assessed by Addenbrooke's Cognitive Examination Revised (ACE-R). Using mediation models, we evaluated the mediation role of parents' educational level, reading time (RT), and physical activity time (PAT) in the years of education (IYE) and cognitive performance.Results: People who reported having lived in an urban area during their childhood are estimated to have, on average, 2.085 years more formal education than those who lived in rural areas. In addition, 49% of cognitive performance scores are explained by the mediation effect of reading and physical activity time in the IYE. This implies that higher levels of education, mediated by RT and PAT per week, are 1.596 units associated with higher scores on the ACE-R.Conclusion: Despite the fact that nonmodifiable factors (i.e., childhood residence area, parents' educational level) seem to exert an effect on older adults' cognition, their influence is mediated by other factors that are indeed modifiable (i.e., reading time, physical activity engagement). In this sense, lifestyle changes could help prevent or decrease the risk of cognitive impairment and reduce the disease's impact on vulnerable environments in Latin American and Caribbean countries. [ABSTRACT FROM AUTHOR]

Sex as a biological variable appears to contribute to the multifactorial etiology of Alzheimer's disease. We tested sex-based interactions between cerebrovascular function and APOE4 genotype on resistance and resilience to brain pathology and cognitive executive dysfunction in cognitively-normal older adults. Female APOE4 carriers had higher amyloid-β deposition yet achieved similar cognitive performance to males and female noncarriers. Further, female APOE4 carriers with robust cerebrovascular responses to exercise possessed lower amyloid-β. These results suggest a unique cognitive resilience and identify cerebrovascular function as a key mechanism for resistance to age-related brain pathology in females with high genetic vulnerability to Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background: Mild cognitive impairment (MCI) is a heterogeneous condition. Idiopathic REM sleep behavior disorder (iRBD) can be associated with MCI (MCI-RBD).Objective: To investigate neuropsychological and brain metabolism features of patients with MCI-RBD by comparison with matched MCI-AD patients. To explore their predictive value toward conversion to a full-blown neurodegenerative disease.Methods: Seventeen MCI-RBD patients (73.6±6.5 years) were enrolled. Thirty-four patients with MCI-AD were matched for age (74.8±4.4 years), Mini-Mental State Exam score and education with a case-control criterion. All patients underwent a neuropsychological assessment and brain 18F-FDG-PET. Images were compared between groups to identify hypometabolic volumes of interest (MCI-RBD-VOI and MCI-AD-VOI). The dependency of whole-brain scaled metabolism levels in MCI-RBD-VOI and MCI-AD-VOI on neuropsychological test scores was explored with linear regression analyses in both groups, adjusting for age and education. Survival analysis was performed to investigate VOIs phenoconversion prediction power.Results: MCI-RBD group scored lower in executive functions and higher in verbal memory compared to MCI-AD group. Also, compared with MCI-AD, MCI-RBD group showed relative hypometabolism in a posterior brain area including cuneus, precuneus, and occipital regions while the inverse comparison revealed relative hypometabolism in the hippocampus/parahippocampal areas in MCI-AD group. MCI-RBD-VOI metabolism directly correlated with executive functions in MCI-RBD (p = 0.04). MCI-AD-VOI metabolism directly correlated with verbal memory in MCI-AD (p = 0.001). MCI-RBD-VOI metabolism predicted (p = 0.03) phenoconversion to an alpha-synucleinopathy. MCI-AD-VOI metabolism showed a trend (p = 0.07) in predicting phenoconversion to dementia.Conclusion: MCI-RBD and MCI-AD showed distinct neuropsychological and brain metabolism profiles, that may be helpful for both diagnosis and prognosis purposes. [ABSTRACT FROM AUTHOR]

Background: Altered cell homeostasis, seen in cognitive decline and frailty, leads to cell death and turnover, releasing circulating cell-free DNA (ccf-DNA).Objective: The goal of this study is to determine if serum genomic cell-free DNA (ccf-gDNA) is associated with physical and cognitive decline in older adults.Methods: We used serum from 631 community-dwelling individuals from the Religious Orders Study or Rush Memory and Aging Project who were without cognitive impairment at baseline. ccf-gDNA fragments in serum were quantified using digital PCR. An array of cognitive and physical traits, risk of dementia, global cognition, and frailty at or nearest the time of blood draw were regressed on ccf-DNA, with adjustment for age, sex, race, and education.Results: Cross-sectionally, higher ccf-gDNA levels were associated with lower global cognition score and slower gait speed at the evaluation nearest to blood draw. Higher ccf-gDNA levels were associated with increased odds of incident dementia (OR 1.27, 95% CI 1.05, 1.54). Longitudinally, higher levels of ccf-gDNA were associated with steeper general cognitive decline and worsening frailty over eight years of follow up.Conclusion: This study demonstrates that ccf-gDNA fragments have utility for identifying persons at higher risk of developing dementia and worsening cognition and frailty. [ABSTRACT FROM AUTHOR]

Background: There has been renewed interest in the deteriorating effects of sub-threshold amyloid-β (Aβ) accumulation in Alzheimer's disease (AD). Despite evidence suggesting a synergistic interaction between the APOE ɛ4 allele and Aβ deposition in neurodegeneration, few studies have investigated the modulatory role of this allele in sub-threshold Aβ deposition during the preclinical phase.Objective: We aimed to explore the differential effect of the APOE ɛ4 carrier status on the association between sub-threshold Aβ deposition, cortical volume, and cognitive performance in cognitively normal older adults (CN).Methods: A total of 112 CN with sub-threshold Aβ deposition was included in the study. Participants underwent structural magnetic resonance imaging, [18F] flutemetamol PET-CT, and a neuropsychological battery. Potential interactions between APOE ɛ4 carrier status, Aβ accumulation, and cognitive function for cortical volume were assessed with whole-brain voxel-wise analysis.Results: We found that greater cortical volume was observed with higher regional Aβ deposition in the APOE ɛ4 carriers, which could be attributed to an interaction between the APOE ɛ4 carrier status and regional Aβ deposition in the posterior cingulate cortex/precuneus. Finally, the APOE ɛ4 carrier status-neuropsychological test score interaction demonstrated a significant effect on the gray matter volume of the left middle occipital gyrus.Conclusion: There might be a compensatory response to initiating Aβ in APOE ɛ4 carriers during the earliest AD stage. Despite its exploratory nature, this study offers some insight into recent interests concerning probabilistic AD modeling, focusing on the modulating role of the APOE ɛ4 carrier status during the preclinical period. [ABSTRACT FROM AUTHOR]

Background: The relationship between grip strength and cognitive function remains no consensus in the older adults.Objective: To investigate the association of grip strength with cognitive function and cognitive performance in different domains.Methods: Participants of the present cross-sectional study were from the National Health and Nutrition Examination Survey 2011-2014. Grip strength was measured by grip dynamometer, and combined handgrip strength was the sum of the largest reading from each hand. Four cognitive domains (immediate and delayed memory, language, and attention) were assessed by a set of neuropsychological tests. The subjective cognitive decline was determined via self-report.Results: Among 2,618 participants, combined grip strength was positively associated with scores on global cognitive function and each cognitive domain after controlling for demographic characteristics, lifestyle factors, and history of disease. In addition, compared to those with grip strength < 46.7 kg, participants with grip strength≥75.3 kg had odds ratios of 0.36 (95% CI: 0.21 to 0.63) for poor global cognitive function, 0.66 (95% CI: 0.38 to 1.13) for poor immediate memory, 0.53 (95% CI: 0.30 to 0.93) for poor delayed memory, 0.48 (95% CI: 0.27 to 0.86) for poor language function, 0.20 (95% CI: 0.11 to 0.35) for poor attention, and 0.36 (95% CI: 0.18 to 0.73) for subjective cognitive decline in fully adjusted model.Conclusion: Older adults with higher grip strength were significantly associated with better performance on cognition function included global and various domains such as memory, language, attention, and subjective cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Multidomain interventions which incorporate exercise and dietary supplementation to target both cognitive and physical health domains may be an important approach to delay cognitive decline.Objective: The Protein Omega-3 aNd vitamin D Exercise Research (PONDER) study investigated the effects of a 6-month multifaceted intervention in community-dwelling older adults with subjective memory impairment on cognition (primary outcome), physical function, and body composition with a further 6-month follow up for cognition (secondary outcomes).Methods: Single-center, community-based, parallel-group, randomized, double-blind placebo-controlled trial involving a 6-month multifaceted intervention with a further follow-up at 12 months. A total of 147 participants [mean age 70.2 years (SD 6.1), 70% female] were randomized to a multimodal exercise program consisting of twice-weekly supervised resistance and aerobic training, combined with a daily omega-3 (900 mg EPA, 600 mg DHA), vitamin D (1000 IU) and protein (20 g) supplement (n = 73), or a control condition (n = 74) comprising stretching/flexibility sessions combined with a placebo. The primary outcome was a composite CogState measure and Trail-Making Test B-A.Results: There were no significant between-group differences in the change of cognition at 6 or 12 months or physical function outcomes at 6 months, but the intervention significantly improved total lean mass compared to controls [0.72 kg (95% CI 0.26-1.19), p = 0.001].Conclusion: A multi-faceted intervention including an omega-3, vitamin D and protein-enriched supplement with twice-weekly exercise training did not provide any benefits to cognitive or physical function in older adults with subjective memory impairment, despite improvements in lean mass. [ABSTRACT FROM AUTHOR]

Background: The relationship between serum folate status and cognitive functions is still controversial.Objective: To evaluate the association between serum tetrahydrofolate and cognitive functions.Methods: A total of 3,132 participants (60-80 years old) from the 2011-2014 NHANES were included in this cross-sectional study. The primary outcome measure was cognitive function assessment, determined by the Consortium to Establish a Registry for Alzheimer's Disease Word Learning Test (CERAD-WL), CERAD-Delayed Recall Test (CERAD-DR), Animal Fluency Test (AF), Digit Symbol Substitution Test (DSST), and global cognitive score. Generalized linear model (GLM), multivariate logistic regression models, weighted generalized additive models (GAM), and subgroup analyses were performed to evaluate the association between serum tetrahydrofolate and low cognitive functions.Results: In GLM, and the crude model, model 1, model 2 of multivariate logistic regression models, increased serum tetrahydrofolate was associated with reduced cognitive functions via AF, DSST, CERAD-WL, CERAD-DR, and global cognitive score (p < 0.05). In GAM, the inflection points were 1.1, 2.8, and 2.8 nmol/L tetrahydrofolate, determined by a two-piece wise linear regression model of AF, DSST, and global cognitive score, respectively. Also, in GAM, there were no non-linear relationship between serum tetrahydrofolate and low cognitive functions, as determined by CERAD-WL or CERAD-DR. The results of subgroup analyses found that serum tetrahydrofolate levels and reduced cognitive functions as determined by AF had significant interactions for age and body mass index. The association between high serum tetrahydrofolate level and reduced cognitive functions as determined using DSST, CERAD-WL, CERAD-DR, or global cognitive score had no interaction with the associations between cognition and gender, or age, or so on.Conclusion: High serum tetrahydrofolate level is associated with significantly reduced cognitive function. [ABSTRACT FROM AUTHOR]

Background: Few studies have examined the associations between personality facets and dementia risk and rarely included individuals from rural settings or with low education.Objective: To examine the association between personality and the risk of cognitive impairment.Methods: Participants (N = 1,668; age 50 to 94 at baseline; 56.4% women; 86.5% less than high school diploma) were from a rural region of Sardinia (Italy) who completed the Revised NEO Personality Inventory (NEO-PI-R) during the first wave (2001-2004) and the Mini-Mental State Examination (MMSE) at waves two to five (2005-2021). Cox regression was used to test personality and covariates as predictors of cognitive impairment based on MMSE education-adjusted cutoffs.Results: During the up to 18-year follow-up (M = 10.38; SD = 4.76), 187 individuals (11.2%) scored as cognitively impaired. Participants with higher neuroticism (particularly the depression facet [HR = 1.22, 95% CI = 1.06-1.40]), and lower agreeableness (particularly the modesty facet [HR = 0.83, 95% CI = 0.71-0.97]) and lower conscientiousness (particularly the dutifulness facet [HR = 0.78, 95% CI = 0.67-0.92]) were at higher risk of cognitive impairment. Lower warmth ([HR = 0.75, 95% CI = 0.65-0.87], facet of extraversion) and ideas ([HR = 0.76, 95% CI = 0.65-0.89], facet of openness) were also associated with increased risk of impairment. These associations were virtually unchanged in models that accounted for other risk factors, including smoking, depression, obesity, hypertension, diabetes, and apolipoprotein E (APOE) ɛ4 carrier status. Across the five domains, sex and the APOE variant did not moderate the associations.Conclusion: In a sample with demographic characteristics underrepresented in dementia research, this study identifies personality domains and facets most relevant to the risk of cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: The prevalence of mild cognitive impairment (MCI) continues to increase due to population aging. Exercise has been a supporting health strategy that may elicit beneficial effects on cognitive function and prevent dementia.Objective: This study aimed to examine the effects of aerobic, resistance, and multimodal exercise training on cognition in adults aged > 60 years with MCI.Methods: We searched the Cochrane Library, PubMed, and Embase databases and ClinicalTrials.gov (https://clinicaltrials.gov) up to November 2021, with no language restrictions. We included all published randomized controlled trials (RCTs) comparing the effect of exercise programs on cognitive function with any other active intervention or no intervention in participants with MCI aged > 60 years.Results: Twelve RCTs were included in this review. Meta-analysis results revealed significant improvements in resistance training on measures of executive function (p < 0.05) and attention (p < 0.05); no significant differences were observed between aerobic exercise and controls on any of the cognitive comparisons.Conclusion: Exercise training had a small beneficial effect on executive function and attention in older adults with MCI. Larger studies are required to examine the effects of exercise and the possible moderators. [ABSTRACT FROM AUTHOR]